Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disease that attacks nerve cells in the brain and the spinal cord, and ultimately is fatal. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. As the motor neurons degenerate, they can no longer send impulses to the muscle fibers that provide muscle movement. The progressive degeneration of the motor neurons in ALS eventually leads to their death. When the motor neurons die, the ability of the brain to initiate and control muscle movement is lost. With all voluntary muscle action affected, patients in the later stages of the disease become totally paralyzed. However, for the vast majority of people their minds remain unaffected.
Early symptoms of ALS often include increasing muscle weakness, especially involving muscles in the arms and legs, and in muscles related to speech, swallowing and breathing. When the muscles no longer receive messages from the motor neurons, the muscles begin to atrophy (waste away).
There are several approaches to treating ALS and its symptoms. However, the only FDA approved medication is Riluzol (Rilutek), which is administered systemic. Riluzol is neuro-protective and inhibits the pre-synaptic release of glutamate, the most important neurotransmitter, and influences the activation of sodium channels. However, systemic administration of neurotropic growth factors is limited due to side effects and to the limited control to gain a specific concentration of effective agents in the target region. Other treatments for ALS involve neurotrophic growth factors or combination therapies with agents from different families of neurotrophic growth factors and/or Riluzol and/or anti-oxidants (e.g., vitamin E).
Recent studies imply the importance of influencing the local concentration of neurotropic growth factors in the central nervous system. Therefore, the agents can be infused directly to target regions or into the cerebrospinal fluid.
Methods of administering a drug or other material to a target part of the body are known in the art. For example, U.S. Pat. No. 6,026,316 discloses a method for targeted drug delivery into a living patient using magnetic resonance (MR) imaging. The method uses MR imaging to track the location of drug delivery and estimate the rate of drug delivery. More particularly, an MR-visible drug delivery device is positioned at a target site to deliver a diagnostic or therapeutic drug solution into the tissue. The spatial distribution kinetics of the injected or infused drug agent are monitored quantitatively and non-invasively using water proton directional diffusion MR imaging to establish the efficacy of drug delivery at a targeted location.
U.S. Pat. No. 5,720,720 discloses a method of high-flow microinfusion that provides convection-enhanced delivery of agents into the brain and other solid tissue structures. The method involves positioning the tip of an infusion catheter within a tissue structure, and supplying an agent through the catheter while maintaining a pressure gradient from the tip of the catheter during infusion. The method can be used to deliver various drugs, protein toxins, antibodies for treatment or imaging, proteins in enzyme replacement therapy, growth factors in the treatment of various neurodegenerative disorders and viruses and gene therapy.
U.S. Pat. No. 5,735,814 discloses techniques for infusing drugs into the brain to treat neurodegenerative disorders by an implantable pump and catheter. The drugs are capable of altering the level of excitation of neurons in the brain. A sensor is used to detect an attribute of the nervous system which reflects the hyperexcitation of the nerve cells projecting onto the degenerating nerve cells, and a microprocessor algorithm analyzes the output from the sensor in order to regulate the amount of drug delivered to the brain.
Finally, U.S. Pat. No. 6,549,803 discloses the movement of material in an organism, such as a drug injected into a brain. The movement is modeled by a uniformly structured field of static constants governing transport by moving fluid and diffusion within the fluid. This supports planning of material introduction, (e.g., infusion, perfusion, retroperfusion, injections, etc.) to achieve a desired distribution of the material, continuing real-time feedback as to whether imaged material is moving as planned and will be distributed as desired, and real-time plan modification to improve results.